Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma

BACKGROUND Helicobacter pylori(H.pylori)is a widespread microorganism related to gastric adenocarcinoma(AC).In contrast,it has been reported that an inverse association exists between H.pylori infection and esophageal carcinoma.The mechanisms underlying this supposedly protective effect remain controversial.AIM To determine the prevalence of H.pylori infection in esophageal carcinoma patients,we performed a retrospective observational study of esophageal tumors diagnosed in our hospital.METHODS We retrospectively reviewed the prevalence of H.pylori infection in a cohort of patients diagnosed with esophageal carcinoma.Concomitant or previous proton pump inhibitor(PPI)usage was also recorded.RESULTS A total of 89 patients with esophageal carcinoma(69 males,77.5%),with a mean age of 66 years(range,26-93 years)were included.AC was the most frequent pathological variant(n=47,52.8%),followed by squamous cell carcinoma(n=37,41.6%).Fourteen ACs(29.8%)originated in the gastroesophageal junction and 33(70.2%)in the esophageal body.Overall,54 patients(60.7%)presented at stages III and IV.Previous H.pylori infection occurred only in 4 patients(4.5%),3 with AC(6.3%of all ACs)and 1 with squamous cell carcinoma(2.7%of all squamous cell tumors).All patients with previous H.pylori infection had stage III-IV.Only one patient had received prior H.pylori eradication therapy,whereas 86(96.6%)had received previous or concomitant PPI treatment.CONCLUSION In our cohort of patients,and after histologic evaluation of paraffin-embedded primary tumors,we found a very low prevalence of previous H.pylori infection.We also reviewed the medical history of the patients,concluding that the majority had received or were on PPI treatment.The minimal prevalence of H.pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis

BACKGROUND Difficulty in obtaining tetracycline,increased adverse reactions,and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple therapy.Therefore,the search for new alternative drugs has become one of the research hotspots.In recent years,minocycline,as a semisynthetic tetracycline,has demonstrated good potential for eradicating Helicobacter pylori(H.pylori)infection,but the systematic evaluation of its role remains lacking.AIM To explore the efficacy,safety,and compliance of minocycline in eradicating H.pylori infection.METHODS We comprehensively retrieved the electronic databases of PubMed,Embase,Web of Science,China National Knowledge Infrastructure,SinoMed,and Wanfang database as of October 30,2023,and finally included 22 research reports on H.pylori eradication with minocycline-containing regimens as per the inclusion and exclusion criteria.The eradication rates of H.pylori were calculated using a fixed or a random effect model,and the heterogeneity and publication bias of the studies were measured.RESULTS The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall H.pylori eradication rates,reaching 82.3%[95%confidence interval(CI):79.7%-85.1%]in the intention-to-treat analysis and 90.0%(95%CI:87.7%-92.4%)in the per-protocol analysis.The overall safety and compliance of the minocycline-containing regimens were good,demonstrating an overall incidence of adverse reactions of 36.5%(95%CI:31.5%-42.2%).Further by traditional meta-analysis,the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse effects.Most of the adverse reactions were mild to moderate and well-tolerated,and dizziness was relatively prominent in the minocycline-containing regimens(16%).CONCLUSION The minocycline-containing regimens demonstrated good efficacy,safety,and compliance in H.pylori eradication.Minocycline has good potential to replace tetracycline for eradicating H.pylori infection.

Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

Polio eradication surveillance in Sri Lanka,2019-2023

Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,2023.The results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and socio-demographics.Data was analyzed using descriptive statistics.Results:A total of 2141 stool samples from 1644 cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)surveillance.Both polioviruses(19/1644,1.15%)and non-polio enteroviruses(73/1644,4.44%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus isolated.Wild polioviruses or circulating VDPVs were not detected among the cases.During all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14 days of receipt,ensuring timely reporting as per global guidelines.Conclusions:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance indicators.Non-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.

Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional therapy.In areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local efficacy.In this study we assess efficacy of HDADT therapy for H.pylori eradication in an Irish cohort.AIM To assess the efficacy of HDADT therapy for H.pylori eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with H.pylori.METHODS All patients testing positive for H.pylori in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 months.Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered positive.Patient demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior H.pylori treatment.RESULTS One hundred and ninety-eight patients were identified with H.pylori infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing.In all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 years.Overall,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of treatment.The groups were statistically similar.Self-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug reactions.Overall the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication status.CONCLUSION Overall eradication rates with HDADT were disappointing.Despite being a simple and possibly better tolerated regime,these results do not support its routine use in a high dual resistance country.Further investigation of other regimens to achieve the>90%eradication target is needed.

外泌体中miR-181a-3p通过UPR/ERAD通路轴调控肺癌对安罗替尼的耐药性

目的探讨外泌体中miR-181a-3p通过未折叠蛋白反应(UPR)/内质网相关蛋白降解(ERAD)通路轴调控肺癌对安罗替尼的耐药性。方法选取人非小细胞肺癌细胞HCC827进行培养,并使用梯度浓度的安罗替尼持续处理诱导安罗替尼耐药性HCC827细胞(HCC827/Anl细胞),对细胞进行转染,分为空白组、对照组及miR-181a-3p inhibitor组。qRT-PCR检测miR-181a-3p表达。MTT法检测HCC827/Anl细胞活性。流式细胞术检测HCC827/Anl细胞凋亡情况。Transwell法检测HCC827/Anl细胞迁移、侵袭情况。Western blot检测UPR/ERAD通路相关蛋白表达。双荧光素酶报告检测miR-181a-3p、eIF2α、HRD1关系。结果空白组与对照组细胞增殖率、侵袭、迁移细胞数比较,差异无统计学意义(P>0.05);与空白组、对照组比较,miR-181a-3p inhibitor组细胞增殖率、侵袭、迁移细胞数明显较低(P<0.05)。对照组与miR-181a-3p inhibitor组eIF2α-MUT、HRD1-MUT无明显差异(P>0.05);但与对照组对比,miR-181a-3p inhibitor组eIF2α-WT、HRD1-WT明显降低(P<0.05)。结论肺癌耐安罗替尼细胞中miR-181a-3p表达明显上调,而miR-181a-3p可能通过外泌体包裹转运激活UPR/ERAD通路轴调控肺癌耐药细胞的增殖、侵袭及迁移,从而增强肺癌对安罗替尼的耐药性。

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(H.pylori)is increasing in severity,and successful eradication is essential.Presently,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment histories.AIM To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided therapy.METHODS We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023.Participants underwent a string test after an overnight fast.The gastric juice was obtained and transferred to vials containing storage solution.Subsequently,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the study.Based on these results,the participants were administered susceptibility-guided treatment.Efficacy was compared with that of the empiric treatment group.RESULTS A total of 132 individuals tested positive for the H.pylori ureA gene by qPCR technique.CLA resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,respectively.The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,respectively.The eradication rates of these two treatment strategies were significantly different in both ITT(P=0.001)and PP(P=0.012)analyses.CONCLUSION H.pylori presented high secondary resistance rates to CLA and LFX.For patients with previous treatment failures,treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Efficacy and safety of low-dose tetracycline,amoxicillin quadruple therapy in Helicobacter pylori infection:A retrospective single center study

BACKGROUND Helicobacter pylori(H.pylori)eradication rates have declined with the rise of antibiotic-resistant strains in recent years.Although highly effective with a low prevalence of resistance,standard dose tetracycline is associated with frequent adverse events.The efficacy and safety of low-dose tetracycline as part of tetra-cycline and amoxicillin-containing bismuth quadruple therapy are not well described.AIM To compare the efficacy and safety of low-dose compared to standard dose tetracycline with combined amoxicillin-containing bismuth quadruple therapy in patients with H.pylori infection.METHODS Consecutive patients with H.pylori infection receiving tetracycline,amoxicillin,proton pump inhibitor,and bismuth for 14 days at Sir Run Run Shaw Hospital(1/2022-6/2023)were evaluated.The low-dose tetracycline group received tetracycline 500 mg twice daily(bid)while the standard dose group received 750 mg bid or 500 mg three times daily(tid).Primary endpoints were H.pylori eradication rate and treatment-related adverse events.

Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.

Role of high-dose amoxicillin dual therapy for Helicobacter pylori eradication in an Irish cohort:A prospective study

Helicobacter pylori(H.pylori)infections may cause chronic gastritis,peptic ulcer disease,gastric cancers,and other conditions outside of the gastrointestinal tract.Hence,it is important to diagnose and treat it early.H.pylori is resistant to certain drugs in traditional eradication therapy,so alternative therapy protocols are needed,such as high-dose amoxicillin dual therapy(HDADT).This article aims to comment on a recent paper by Costigan et al in the World Journal of Clinical Cases.In this study,the authors recruited 139 patients diagnosed with H.pylori,all treated with HDADT.Of these,93 were treatment-naïve and 46 had received at least one alternative treatment in the past.Four weeks after the end of the treatment,the urea breath test was administered to estimate the eradication rate.The total eradication rate was 56%(78/139),62%for the treatment-naïve arm and 43%for the previous treatment arm,thus indicating a lower success rate for the arm that had previously received a different treatment regimen.In conclusion,a therapeutic approach with first-line HDADT may potentially be a better treat-ment,but the results are not sufficient to recommend the use of this regimen in a country with high levels of dual resistance.

Transformed gastric mucosa-associated lymphoid tissue lymphoma originating in the colon and developing metachronously after Helicobacter pylori eradication:A case report

BACKGROUND Helicobacter pylori(H.pylori)eradication treatment for primary gastric mucosaassociated lymphoid tissue(MALT)lymphoma has already been established.However,t(11;18)(q21;q21)/API2-MALT1 translocation-positive lesions are a type of primary gastric MALT lymphoma in which a response to eradication treatment is difficult to achieve.In addition,trisomy 18 may be associated with diffuse large B-cell lymphoma(DLBCL)transformation of gastric MALT lymphoma.CASE SUMMARY A 66-year-old man was diagnosed with MALT lymphoma in the ascending colon by colonoscopy and biopsy.Two years later,esophagogastroduodenoscopy revealed chronic atrophic gastritis that was positive for H.pylori,and eradication treatment was administered.Two years and nine months later(at the age of 70),a new ulcerative lesion suggestive of MALT lymphoma appeared in the gastric body,and six months later,a similar lesion was also found in the fundus.One year later(4 years and 3 months after H.pylori eradication),at the age of 72,the lesion in the gastric body had become deeper and had propagated.A biopsy revealed a pathological diagnosis of DLBCL.Both MALT lymphoma lesions in the ascending colon and DLBCL lesions in the stomach were positive for the t(11;18)(q21;q21)/API2-MALT1 translocation,and trisomy 18q21 was also detected.After 6 courses of R-CHOP(rituximab,cyclophosphamide,doxorubicin,vincristine and prednisone)chemotherapy,all of the above lesions disappeared[complete remission(CR)],and CR has been maintained for more than 3 years.In addition,both the colonic and gastric lesions were proven to have the same clonality.CONCLUSION Because the patient had a MALT1 translocation with trisomy 18q21,it was thought that this gastric MALT lymphoma developed independently of H.pylori infection and progressed.

Eradication Treatment of Helicobacter pylori Infection: Evaluation of Therapeutic Strategies in N’Djamena

Background: Helicobacter pylori (Hp) infection is the most widespread bacterial infection in the world. The infection is generally acquired in childhood, but can persist into adulthood. Eradication therapy has undergone several modifications. The aim of this study was to evaluate the different therapeutic strategies used in the eradication of Helicobacter pylori infection in the Centre Hospitalier Universitaire La Reference Nationale of N’Djaména. Patients and Methods: This was a prospective, descriptive analytical study spread over one year, from September 2021 to September 2022. Patients at least 15 years of age presenting with dyspeptic symptoms, seen consecutively in a hepato-gastroenterology consultation and with a positive stool test for H. pylori infection, were included in the study. Equally, 1/3 of patients were treated with dual or triple therapy. The remaining third received quadritherapy. Results: A total of 268 patients were included in the study (mean age 38.40 ± 14.66 with extremes of 16 and 80 years). Males predominated in 58% of cases. Overall therapeutic efficacy was 88.9%. According to different therapeutic strategies, efficacy was 90.75% for dual therapy with PPI (Rabeprazole) and Amoxicillin. On the other hand, efficacy was 87% and 88.88% for PPI-based triple therapy and dual antibiotic therapy, and for PPI-based quadruple therapy and triple antibiotic therapy. Conclusion: H. pylori infection is a common disease in Chad. Dual therapy with rabeprazole combined with a high dose of amoxicillin over a period of at least two weeks showed similar if not better efficacy than triple or quadruple therapy.

Impacts of Helicobacter pylori infection and eradication on gastrointestinal microbiota:An up-to-date critical review and future perspectives

Helicobacter pylori(H.pylori)infects approximately half of the population worldwide and causes chronic gastritis,peptic ulcers,and gastric cancer.Test-and-treat strategies have been recommended for the prevention of H.pylori-associated diseases.Advancements in high-throughput sequencing technologies have broadened our understanding of the complex gastrointestinal(GI)microbiota and its role in maintaining host homeostasis.Recently,an increasing number of studies have indicated that the colonization of H.pylori induces dramatic alterations in the gastric microbiota,with a predominance of H.pylori and a reduction in microbial diversity.Dysbiosis of the gut microbiome has also been observed after H.pylori infection,which may play a role in the development of colorectal cancer.However,there is concern regarding the impact of antibiotics on the gut microbiota during H.pylori eradication.In this review,we summarize the current literature concerning how H.pylori infection reshapes the GI microbiota and the underlying mechanisms,including changes in the gastric environment,immune responses,and persistent inflammation.Additionally,the impacts of H.pylori eradication on GI microbial homeostasis and the use of probiotics as adjuvant therapy are also discussed.The shifts in the GI microbiota and their crosstalk with H.pylori may provide potential targets for H.pylori-related gastric diseases and extragastric manifestations.

Evaluation of the “Helicobacter pylori” Eradication Rate by Bismuth Quadritherapy or Concomitant Quadritherapy in Black Africans

Introduction: Gastric infection by “Helicobacter pylori” remains a topical issue due to the evolving scientific data concerning its pathophysiology, the diseases and pathologies concerned, which now extend beyond the gastric or digestive sphere, and the treatment methods faced with the development of antibiotic resistance. Diagnosis of infection involves two inseparable aspects: identification of the bacterium itself and identification of the endoscopic and histological lesions caused by the bacterium. Objective: To evaluate the rate of eradication of Helicobacter pylori infection by bismuth quadruple therapy and concomitant treatment. Patients and methods: This was a prospective, cross-sectional, analytical study of all outpatients in the hepato-gastroenterology department during the study period from 1 January 2022 to 30 November 2023. All patients had undergone oeso-gastroduodenal fibroscopy and the diagnosis was made by histological examination of the gastric biopsy. Results: Our 113 patients comprised 68 men and 46 women. The sex ratio was 1.48 in favour of men. The mean age of our patients was 40.28 years, with extremes of 13 and 80 years. The clinical signs that prompted oeso-gastroduodenal fibroscopy were as follows: epigastralgia (69.91%), dyspepsia (14.16%), vomiting (7.08%), gastro-oesophageal reflux (6.19%) and altered general condition with weight loss (2.65%). The endoscopic lesions were: gastropathy (antral, fundic and diffuse: antro-fundial) (69.02%), bulbar ulcer (6.19%), gastric ulcer (5.31%). Helicobacter pylori infection was associated with chronic gastritis in all our patients;it was mild in 50%, moderate in 41% and severe in 9%. The eradication rate of Helicobacter pylori according to the treatment protocol used was 92.30% for bismuth quadruple therapy and 94.12% for concomitant quadruple therapy. Conclusion: The eradication rate of Helicobacter pylori in our study was 92.30% and 94.12% respectively for bismuth quadritherapy and concomitant therapy. Therapeutic compliance was good in 89.60% for all protocols combined, despite the occurrence of side effects in 36.22% of cases.

Access to Financial Services——An Analysis from the Human Rights Perspective

There is a broad connection between finance and human rights,with finance having both positive and negative impacts on human rights.Everyone has a need for access to financial services.Documents in both the international human rights and international finance fields address the relationship between financial services and human rights.Among financial services,microcredit and inclusive finance have the closest connection to human rights and potentially the greatest impact on human rights.Access to financial services promotes economic,social,and cultural rights as well as the rights of specific groups.The conditions for access to financial services to promote human rights require the state to assume obligations to recognize,respect,protect,and fulfill the need for individuals to access financial services,and to ensure the availability,accessibility,acceptability,and adaptability of basic financial services.Access to financial services has played a significant role in China’s comprehensive victory in the battle of poverty alleviation,providing valuable experience for the international community in poverty eradication,achieving sustainable development goals,and protecting and promoting human rights.

扶正口服液对诱导性癌症恶病质裸鼠骨骼肌中ERAD/ERSIA通路的影响

目的探究扶正口服液对癌症恶病质(cancer cachexia,CC)裸鼠骨骼肌内质网应激相关性降解(ER-associated degradation,ERAD)/内质网应激性凋亡(endoplasmic reticulum stress induced apoptosis,ERSIA)信号通路的影响。方法选取36只6~7周龄BALB/c-nu SPF级裸鼠建立脾虚证模型,随机抽取12只均分成A组(正常裸鼠生理盐水灌胃56 d)、B组(正常裸鼠扶正口服液灌胃56 d);剩余24只进行CC造模,分为C组(CC后生理盐水灌胃14 d)、D组(CC后扶正口服液灌胃14 d)、E组(CC后生理盐水灌胃28 d)、F组(CC后扶正口服液灌胃28 d)。比较各组裸鼠的体质量、摄食量、肿瘤体积、骨骼肌病理变化。通过Western blot、RT-PCR检测扶正口服液对不同CC阶段裸鼠骨骼肌中ERSIA通路中CCAAT增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein-homologous protein,CHOP)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)表达水平;ERAD通路中X盒结合蛋白1(X-box binding protein-1,XBP1)、内质网跨膜蛋白激酶1(inositol requiring enzyme-1,IRE1)、内质网相关降解蛋白1(Derlin-1)、滑膜细胞凋亡抑制物1(synovial apoptosis inhibitor-1,SYVN1)表达水平。结果与A、B组比较,C、D、E、F组摄食量均下降(P<0.05);与C组比较,D组摄食量增加,E、F组摄食量下降(P<0.05);与D组比较,E、F组摄食量下降(P<0.05);与E组比较,F组摄食量增加(P<0.05)。与A、B组比较,第6周C、D组体质量下降(P<0.05),第8周E、F组体质量下降(P<0.05);与C组比较,第6周D组体质量增加(P<0.05);与E组比较,第8周F组体质量增加(P<0.05)。与C组比较,D组肿瘤体积减小(P<0.05),E组肿瘤体积增大(P<0.05);与E组比较,F组肿瘤体积减小(P<0.05)。与A、B组比较,C、E组裸鼠肌肉组织萎缩,其间隙增大,而D、F组间隙明显缩小,组织萎缩缓解。与A组比较,B组CHOP mRNA,CHOP、p-JNK蛋白表达下降(P<0.05);与B组比较,C组CHOP mRNA,CHOP、p-JNK蛋白表达升高(P<0.05);与C组比较,D组CHOP mRNA,CHOP、p-JNK蛋白表达下降(P<0.05);与E组比较,F组CHOP mRNA,CHOP、p-JNK蛋白表达下降(P<0.05)。与A组比较,B组XBP1、IRE1、Derlin-1、SYVN1蛋白及mRNA表达升高(P<0.05);与B组比较,C组XBP1、Derlin-1、SYVN1蛋白及mRNA表达下降(P<0.05),IRE1 mRNA及蛋白表达升高(P<0.05);与C组比较,D组XBP1、Derlin-1、SYVN1 mRNA及蛋白表达升高(P<0.05),IRE1 mRNA及蛋白表达下降(P<0.05);与E组比较,F组XBP1、IRE1、Derlin-1、SYVN1蛋白及mRNA表达升高(P<0.05)。结论扶正口服液可通过上调骨骼肌中ERAD相关蛋白表达,抑制ERSIA凋亡蛋白表达,以逆转ERAD-ERSIA信号稳态失衡。其改善CC的机制可能与提高肌细胞对ERS的耐受能力并保护肌细胞免于凋亡有关。

糖蛋白折叠质量的监控机制

内质网是一种重要的真核细胞器,糖蛋白的糖基化开始于其中。在内质网中永久性折叠错误糖蛋白或幼稚型糖链糖蛋白,以及突变的糖蛋白被阻止进入高尔基体,而是选择性地被运到胞质,然后在蛋白酶体中被降解。至少两大分子伴侣家族结合蛋白(BiP)和钙联结蛋白(CNX)/钙网蛋白(CRT)参与了糖蛋白折叠的质量控制过程。

内质网压力响应相关的蛋白质降解

内质网相关蛋白质降解途径(ERAD),即蛋白质分泌过程中错误折叠或未折叠的蛋白质在内质网中被识别并逆向运输到细胞质经聚泛素化后由蛋白酶体降解的过程.自从发现该途径后对其机制的阐明一直处于不断探索的阶段.近年来,对ERAD底物识别、逆向运输和泛素化新组分的发现以及新技术的应用,使得该途径的具体分子机制更加清晰.本文全面梳理并综述了内质网应激响应、ERAD降解过程与机理的最新进展,并对模式蛋白底物和最新研究方法进行了总结,以期展示该领域的研究概况.

Adverse events with bismuth salts for Helicobacter pylori eradication:Systematic review and meta-analysis

AIM： To assess the safety of bismuth used in Helicobacter pylori （H pylorl） eradication therapy regimens. METHODS： We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched （up to October 2007） to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppresion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals （CI）.RESULTS： We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth rrelative risk （RR） = 1.01; 95% CI： 0.87-1.16], specific individual adverse events, with the exception of dark stools （RR = 5.06; 95% CI： 1.59-16.12）, or adverse events leading to withdrawal of therapy （RR = 0.86; 95% CI： 0.54-1.37）. CONCLUSION： Bismuth for the treatment of H py/ori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.